Rett syndrome is a developmental disorder of the brain occurring mostly in females characterized by normal early development, followed by a slowing of development resulting in loss of control of the hands, loss of speech, breathing problems, slowed brain and head growth, ambulatory problems, seizures, and mental retardation. Rett syndrome affects approximately 1 in 10,000 live female births. Most cases of Rett syndrome are caused by a mutation in the methyl CpG binding protein 2, or MECP2 gene, on the X chromosome that causes reduced activity or inactivation of MECP2.
MECP2 is a transcriptional repressor that binds to methylated DNA and is present in large quantities in mature nerve cells. MECP2 represses transcription from methylated gene promoters through interaction with histone deacetylase and the corepressor SIN3A. Many of the genes that are known to be regulated by the MECP2 protein play a role in normal brain function, particularly the maintenance of synapses. Mouse studies have demonstrated MECP2 mutations cause defects in synaptic function, especially in synaptic plasticity.